Marilyn B. Escobedo

Part 11: Neonatal Resuscitation 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

2010;126;e1319-e1344; originally published online Oct 18, 2010; Pediatrics COLLABORATORS CHAPTER Sithembiso Velaphi and on behalf of the NEONATAL RESUSCITATION Sam Richmond, Wendy M. Simon, Nalini Singhal, Edgardo Szyld, Masanori Tamura, Chameides, Jay P. Goldsmith, Ruth Guinsburg, Mary Fran Hazinski, Colin Morley, Jeffrey M. Perlman, Jonathan Wyllie, John Kattwinkel, Dianne L. Atkins, Leon Recommendations Resuscitation and Emergency Cardiovascular Care Science With Treatment Neonatal Resuscitation: 2010 International Consensus on Cardiopulmonary http://www.pediatrics.org/cgi/content/full/126/5/e1319 located on the World Wide Web at: The online version of this article, along with updated information and services, is rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Grove Village, Illinois, 60007. Copyright

Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

The following guidelines are a summary of the evidence presented in the 2015 International Consensus on Cardiopulmo nary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR).1,2 Throughout the online version of this publication, live links are provided so the reader can connect directly to systematic reviews on the International Liaison Committee on Resuscitation (ILCOR) Scientific Evidence Evaluation and Review System (SEERS) website. These links are indicated by a combination of letters and numbers (eg, NRP 787). We encourage readers to use the links and review the evidence and appendices. These guidelines apply primarily to newly born infants transitioning from intrauterine to extrauterine life. The recommendations are also applicable to neonates who have completed newborn transition and require resuscitation during the first weeks after birth.3 Practitioners who resuscitate infants at birth or at any time during the initial hospitalization should consider following these guidelines. For purposes of these guidelines, the terms newborn and neonate apply to any infant during the initial hospitalization. The term newly born applies specifically to an infant at the time of birth.3 Immediately after birth, infants who are breathing and crying may undergo delayed cord clamping (see Umbilical Cord Management section). However, until more evidence is available, infants who are not breathing or crying should have the cord clamped (unless part of a delayed cord clamping research protocol), so that resuscitation measures can commence promptly. Approximately 10% of newborns require some assistance to begin breathing at birth. Less than 1% require extensive resuscitation measures,4 such as cardiac compressions and medications. Although most newly born infants successfully transition from intrauterine to extrauterine life without special help, because of the large total number of births, a significant number will require some degree of resuscitation.3 Newly born infants who do not …

Effect of Epidermal Growth Factor on Lung Maturation in Fetal Rabbits

Summary: Injection of epidermal growth factor (EGF) into 24-day rabbit fetuses (5 μg, im or ip) induced accelerated maturation of the lung. On sacrifice at day 27, there was greater distensibility and stability on deflation associated with the appearance of a complement of type II cells approaching that of the rabbit at term. EGF treatment had no demonstrable effect on body weight or lung weight in this group of animals. Saline-injected control fetuses were not affected significantly.Speculation: EGF is capable not only of promoting epithelial cell growth but also differentiation in the fetal rabbit lung. It may be an important hormone in the maturation of the lung and capable of protecting the prematurely delivered fetus against the development of hyaline membrane disease.

2005 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and neonatal patients: Neonatal resuscitation guidelines

THE FOLLOWING GUIDELINES are intended for practitioners responsible for resuscitating neonates. They apply primarily to neonates undergoing transition from intrauterine to extrauterine life. The recommendations are also applicable to neonates who have completed perinatal transition and require resuscitation during the first few weeks to months following birth. Practitioners who resuscitate infants at birth or at any time during the initial hospital admission should consider following these guidelines. The terms newborn and neonate are intended to apply to any infant during the initial hospitalization. The term newly born is intended to apply specifically to an infant at the time of birth. Approximately 10% of newborns require some assistance to begin breathing at birth. Approximately 1% require extensive resuscitative measures. Although the vast majority of newly born infants do not require intervention to make the transition from intrauterine to extrauterine life, because of the large number of births, a sizable number will require some degree of resuscitation. Those newly born infants who do not require resuscitation can generally be identified by a rapid assessment of the following 4 characteristics:

Ventilatory management of infant baboons with hyaline membrane disease: The use of high frequency ventilation

Abstract: We tested the hypothesis that high frequency oscillatory ventilation (HFOV) would result in decreased pulmonary barotrauma in infants with hyaline membrane disease by comparing HFOV at 10 Hz to conventional positive pressure ventilation with continual distending airway pressure (PPV/PEEP) in premature baboons with hyaline membrane disease. Nineteen baboon fetuses were randomized to one of two treatment groups, delivered at 140 ± 2 days, and, after stabilization and instrumentation of PPV/PEEP, placed in their respective ventilator group. Animals on conventional ventilation were managed by adjustment of tidal volume and frequency (to 1 Hz) to keep PaCO2 below 55 and by adjustment of the mean airway pressure. One of the “HFOV” group died of cardiovascular complications before going on HFOV and was eliminated from data analysis. The remaining HFOV baboons survived the 11-day experimental period without evidence of airleak. Six of the 11 prematures treated with PPV/PEEP developed pulmonary interstitial emphysema and/or pneumothorax and five of the animals died within 48 h. The intergroup differences in airleak were significant (p < 0.05). Mean airway pressure (measured at the proximal airway) was higher initially with HFOV but then was lowered more rapidly than in the PPV/PEEP animals. The arterial to alveolar oxygen ratio rose and the FIO2 could be lowered more rapidly with HFOV than with conventional ventilation. These differences reached significance by 20 h. After 60 h there were no significant differences between HFOV and the PPV/PEEP survivors. HFOV resulted in more uniform saccular expansion, higher arterial to alveolar oxygen ratio, less oxygen exposure, and decreased acute barotrauma when compared to PPV/PEEP. Although initially mean airway pressure was in the HFOV animals this was not associated with measurable baroinjury. These data support the efficacy of HFOV in the treatment of prematures with hyaline membrane disease.

A baboon model of bronchopulmonary dysplasia. II. Pathologic features

Abstract A light microscopic (LM), transmission electron microscopic (TEM), and scanning electron microscopic (SEM) study was performed on the lungs from seven baboons delivered by cesarean section prematurely (75% of full gestation) and one at full term. Six of the seven premature baboons pursued a clinical course typical of human hyaline membrane disease (HMD) and/or bronchopulmonary dysplasia (BPD). All the animals were supported with mechanical ventilation and exposed to continuous high levels of inspired oxygen. Three animals died early (⩽3 days) of complications and two demonstrated typical light and electron microscopic lesions of hyaline membrane disease. Three baboons survived ⩾ 8 days and developed pathologically confirmed bronchopulmonary dysplasia, characterized by an altered inflation pattern of atelectasis and overdistension/“emphysema,” bronchial and bronchiolar lesions of necrosis, regenerative hyperplastic and/or squamous metaplastic changes, and peribronchiolar fibrosis and early alveolar wall fibrosis. A striking finding was a hyperplastic/obliterative respiratory bronchiolar lesion, most frequently seen in the atelectatic areas. The lungs of these animals lacked pores of Kohn; a feature shared by a study group of untreated baboons with gestation ages of 109 to 180 days. It is suggested that the lack of collateral ventilation, plus the striking hyperplastic-obliterative airway lesion might explain the characteristic feature of atelectasis. The histopathologic features of this model coincide with with those of BPD in the human neonate, with the exception of the hypertensive vascular changes, which may be a time-related lesion. The pathologic findings further support the premise that the premature baboon will be a very useful model in which the primary etiologic consideration of oxygen toxicity and barotrauma can be separated as to their roles in the causation of bronchopulmonary dysplasia.

A baboon model of bronchopulmonary dysplasia: I. Clinical features

Abstract Investigation in bronchopulmonary dysplasia (BPD) has been seriously hampered by the lack of a suitable animal model. The consistent development of BPD in preterm baboons ( Papio cynocephalus ) with hyaline membrane disease (HMD) who were treated with 95–100% inspired oxygen and supported with mechanical ventilation for more than 1 week is reported. One term (173 days) and nine preterm (134–147 days) pregnancies were delivered by cesarean section with birth weights 495–988 g. Amniotic fluid lecithin: sphingomyelin (L/S) ratios ranged from 0.47 to 1.00. The six animals with L/S ratios ⩽ 0.62 developed HMD. The clinical and radiologic course was indistinguishable from HMD in preterm humans. HMD was confirmed pathologically in two animals dying acutely. One of the remaining four was supported with supplemental oxygen as needed and remains a long-term survivor of HMD. The other three were maintained in 95–100% oxygen. A clinical and radiographic picture similar to that of human BPD developed in each and was pathologically confirmed. The preterm baboon appears to be a suitable animal model for investigation of the etiology, pathophysiology, prevention, therapy, and long-term sequelae of HMD and BPD.

A randomized study of a monoclonal antibody (pagibaximab) to prevent staphylococcal sepsis

BACKGROUND: Pagibaximab, a human chimeric monoclonal antibody developed against lipoteichoic acid, was effective against staphylococci preclinically and seemed safe and well tolerated in phase 1 studies. OBJECTIVE: To evaluate the clinical activity, pharmacokinetics, safety, and tolerability of weekly pagibaximab versus placebo infusions in very low birth weight neonates. PATIENTS AND METHODS: A phase 2, randomized, double-blind, placebo-controlled study was conducted at 10 NICUs. Patients with a birth weight of 700 to 1300 g and 2 to 5 days old were randomly assigned to receive 3 once-a-week pagibaximab (90 or 60 mg/kg) or placebo infusions. Blood was collected for pharmacokinetics, bacterial killing, and safety analyses. Adverse event and clinical outcome data were collected. RESULTS: Eighty-eight patients received pagibaximab at 90 (n = 22) or 60 (n = 20) mg/kg or placebo (n = 46). Groups were not different in demography, mortality, or morbidity. Pagibaximab demonstrated linear pharmacokinetics, a 14.5-day half-life, and nonimmunogenicity. Definite staphylococcal sepsis occurred in 0%, 20%, and 13% (P < .11) and nonstaphylococcal sepsis occurred in 0%, 10%, and 15% (P < .15) of patients in the 90 mg/kg, 60 mg/kg, and placebo groups, respectively. In all patients with staphylococcal sepsis, estimated or observed pagibaximab levels were <500 μg/mL (target level) at infection. CONCLUSIONS: Three once-a-week 90 or 60 mg/kg pagibaximab infusions, in high-risk neonates, seemed safe and well tolerated. No staphylococcal sepsis occurred in infants who received 90 mg/kg. Target levels were only consistently achieved after 2 to 3 doses. Dose optimization should enhance protection.

High-frequency ventilation compared to conventional positive-pressure ventilation in the treatment of hyaline membrane disease in primates.

High-frequency ventilation (HFV) has been suggested as an alternative to conventional positive-pressure ventilation (PPV) in the treatment of infants with hyaline membrane disease (HMD). Using a previously validated primate model of HMD, 15 baboon fetuses were delivered at 75% of gestation and randomly assigned to 1 of 3 ventilator treatment groups: (a) PPV, (b) HFV delivered by an oscillator (HFO), or (c) HFV delivered by a flow interrupter (HFFI). All animals had clinical and radiographic evidence of HMD. At 96 h of life, all animals were sacrificed and clinical and pathologic findings were analyzed. During the first 10 h of the experiment, the HFO animals required higher mean proximal airway pressures than either the HFFI or PPV groups. However, both the HFFI and HFO animals had higher PaO2/PAO2 ratios than the PPV controls, suggesting earlier saccular recruitment. Thus, HFV is as effective as PPV in the treatment of HMD in baboons. Whether it will decrease the risk of bron-chopulmonary dysplasia is not known.

Pulmonary interstitial emphysema in the premature baboon with hyaline membrane disease.

During experiments designed to develop an appropriate ventilatory strategy for high-frequency ventilation (HFV) in the premature baboon with hyaline membrane disease (HMD), we observed the development of pulmonary interstitial emphysema (PIE). Four study groups of 5 animals each received positive-pressure ventilation and positive end-expiratory pressure (PPV/PEEP) or HFV and 1 of 3 sighing techniques. Pathologically, all animals ventilated with PPV/PEEP or HFV with a carefully controlled intermittent sigh developed dilatation of the distal conducting airway and alveolar duct, with poorly expanded pulmonary saccules. The imposition of a sigh with inappropriate timing or excessive volume ruptured the dilated airway walls and caused interstitial air to accumulate. This was evident from the location of striking dilation of the distal airways and pseudocysts in areas of atelectasis. Thus, early in the course of HMD when saccular aeration is minimal, the pathogenesis of PIE is related to airway rather than alveolar rupture.